MADD

Gene Information

Official Symbol: MADD
Official Name: MAP kinase activating death domain
Aliases and Previous Symbols: N/A
Entrez ID: 8567
UniProt: Q8WXG6
Interactions: BioGRID
PubMed articles: Open PubMed
OMIM: Open OMIM

Function Summary

Entrez Summary: Tumor necrosis factor alpha (TNF-alpha) is a signaling molecule that interacts with one of two receptors on cells targeted for apoptosis. The apoptotic signal is transduced inside these cells by cytoplasmic adaptor proteins. The protein encoded by this gene is a death domain-containing adaptor protein that interacts with the death domain of TNF-alpha receptor 1 to activate mitogen-activated protein kinase (MAPK) and propagate the apoptotic signal. It is membrane-bound and expressed at a higher level in neoplastic cells than in normal cells. Several transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008].
UniProt Summary: Plays a significant role in regulating cell proliferation, survival and death through alternative mRNA splicing. Isoform 5 shows increased cell proliferation and isoform 2 shows decreased. Converts GDP-bound inactive form of RAB3A, RAB3C and RAB3D to the GTP-bound active forms. Component of the TNFRSF1A signaling complex: MADD links TNFRSF1A with MAP kinase activation. Plays an important regulatory role in physiological cell death (TNF-alpha-induced, caspase-mediated apoptosis); isoform 1 is susceptible to inducing apoptosis, isoform 5 is resistant and isoform 3 and isoform 4 have no effect. {ECO:0000269|PubMed:11577081, ECO:0000269|PubMed:14716293, ECO:0000269|PubMed:14735464, ECO:0000269|PubMed:15007167, ECO:0000269|PubMed:20937701, ECO:0000269|PubMed:9115275}.

Pfam Domains GO Terms

CRISPR Data

Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)

Global Fraction of Cell Lines Where Essential: 0/739

Tissue	Fraction Of Cell Lines Where Essential
1290807.0	0/1
909776.0	0/1
bile duct	0/28
blood	0/28
bone	0/26
breast	0/33
central nervous system	0/56
cervix	0/4
colorectal	0/17
esophagus	0/13
fibroblast	0/1
gastric	0/16
kidney	0/21
liver	0/20
lung	0/75
lymphocyte	0/16
ovary	0/26
pancreas	0/24
peripheral nervous system	0/16
plasma cell	0/15
prostate	0/1
skin	0/24
soft tissue	0/9
thyroid	0/2
upper aerodigestive	0/22
urinary tract	0/29
uterus	0/5

Essentiality in NALM6

Essentiality Rank: 4756
Expression level (log2 read counts): 6.23

Expression Distribution

DENN
uDENN
dDENN

regulation of Rab protein signal transduction
death receptor binding
protein kinase activator activity
Rab guanyl-nucleotide exchange factor activity
execution phase of apoptosis
regulation of extrinsic apoptotic signaling pathway via death domain receptors
regulation of tumor necrosis factor-mediated signaling pathway
regulation of extrinsic apoptotic signaling pathway
activation of MAPK activity
regulation of cytokine-mediated signaling pathway
regulation of response to cytokine stimulus
regulation of Ras protein signal transduction
positive regulation of MAP kinase activity
activation of protein kinase activity
positive regulation of protein serine/threonine kinase activity
regulation of MAP kinase activity
regulation of small GTPase mediated signal transduction
regulation of apoptotic signaling pathway
regulation of protein serine/threonine kinase activity
positive regulation of protein kinase activity
positive regulation of MAPK cascade
positive regulation of kinase activity
positive regulation of transferase activity
regulation of MAPK cascade
regulation of protein kinase activity
regulation of kinase activity
apoptotic process
regulation of transferase activity
positive regulation of protein phosphorylation
positive regulation of intracellular signal transduction
programmed cell death
positive regulation of phosphorylation
cell death
positive regulation of phosphate metabolic process
positive regulation of phosphorus metabolic process
regulation of cell cycle
positive regulation of protein modification process
positive regulation of catalytic activity
regulation of protein phosphorylation
regulation of apoptotic process